Methods and means to damage pathogenic bacteria in the present are antibiotics which combine all medications that suppress activity of infectious agents such as bacteria, fungi, and protozoa.
However, due to increased drug resistance of infectious agents to the known groups of antibiotics, the problem of development of new antimicrobial drugs has not lost its relevance.
Thus, for example, worldwide there is an increase in tuberculosis incidence rate and increase in mortality observed, caused by drug-resistant pathogens. Resistance to antituberculosis drugs was found in all 35 surveyed countries and regions, indicating that the problem is global.
Polyresistance to antituberculosis drugs is the most difficult form of drug-resistance, known at present. According to WHO, since the early 90-ies in different regions of the planet several outbreaks of multidrug-resistant tuberculosis have been reported.
It is known that molecular iodine can easily pass through bi-lipid cell membranes of microorganisms and penetrate into a cell. Antimicrobial action of iodine compound is due to the ability of iodine (elemental iodine, hypoiodine acid, iodine cation) to interact with NH2-groups of amino acids (lysine, histidine, arginine, etc.), as well as nucleotides (adenine, cytosine, guanine) forming N-iodine derivatives. In addition, there is an oxidation of SH-groups of cysteine taking place, resulting in disruption of protein synthesis. Interaction with phenolic groups of iodine tyrosine leads to breaking of hydrogen bonds in these amino acids. Affecting double carbon bonds of unsaturated fatty acids, iodine thereby changes the properties of lipids.
The ability of iodine to easily penetrate through cell membranes makes its application more valuable for those infections, the main development of which takes place in intracellular structures (brucellosis, clamidiosis, hepatitis, etc.).
There is a known drug Yodomidol, with bactericidal and virucidal activity, containing iodine, potassium or sodium iodide, synthetic water-soluble polymer, natural polymers such as polysaccharides and mono- and oligosaccharides, in the following ratio, g/L:
iodine6-10potassium iodide9-15synthetic water-soluble polymer2-4 natural polymer (polysaccharides) and 8-120mono- and oligosaccharideswaterBalance(KZ 6730B, 16.11.1998).Disadvantage of this drug is its relatively high toxicity.
There is a known virulicidal pharmaceutical product (EP 0978289 A1, Sep. 2, 2000), with antiviral activity, which contains iodine, potassium or sodium iodide, synthetic water-soluble polymer, a mixture of natural mono-, oligo- and polysaccharides and lithium chloride with the following components ratio, g/L:
iodine  0.8-25potassium iodide1.2-38lithium chloride0.1-20synthetic water-soluble polymer0.01-6 mono-, oligo- and polysaccharides  8-400waterBalance
There is a known bactericidal and virucidal pharmaceutical product for prevention and treatment of mono- and mixed infections, including tuberculosis, brucellosis, plague, hepatitis, HIV, containing a pool of proteins and/or halogenated proteins, carbohydrates and/or halogen-derivative carbohydrates, synthetic water-soluble polymer, lithium chloride, potassium or sodium iodide, iodine, water or saline solution in the following ratio (g/L):
pool of proteins and/or halogenated proteinsFrom 0.01 to 200carbohydrates and/or halogen-derivative carbohydratesFrom 0.01 to 450synthetic water-soluble polymerFrom 0.01 to 100lithium chlorideFrom 0.01 to 200potassium or sodium iodideFrom 0.01 to 300iodineFrom 0.01 to 200water or saline solutionto 1 L(KZ 15116A, 15.12.2004).
Bactericidal and virucidal pharmaceutical agent represents a complex physical-chemical system, formed by mono- and polyfunctional ligands (anions, proteins, carbohydrates, synthetic water-soluble polymers) and acids (iodine, alkali metal cations), which is in pseudo-equilibrium state. In this system, there are adjoint complexation, association and dissociation processes taking place. A sequence of processes of acid-base interactions; chemical nature of the polyfunctional ligands (proteins, carbohydrates, water-soluble synthetic polymers) involved in them, the presence in the process of ligands with different molecular weight (e.g. mono-, oligo- and polysaccharides) results in structure formation in the system, and thus it acquires all properties of a colloidal system.
The presence of pharmaceutical iodine in the composition not only enhances bactericidal and virucidal properties due to those of iodine itself, but it also ensures a synergistic effect of each active substance individually and of all of them together present in the agent in balanced concentrations.
This product contains halogen derivative compounds: halogenated proteins and halogenated carbohydrates.
There is a known iodine complex of alkylpolyglycosides (WO 9639839 A1, Dec. 19, 1996) containing (in % wt.) from 0.5 to 30 of iodine; from 0.2 to 14 of iodide in the form of salt; acids or their blends, and from 2 to 85 of sugar surfactant selected from the group of sugars containing alkyl glucose ether, aldobionamide, glycinamide, glyceramide, glyceroglulipoid, fatty polyhydroxy acids amides, alkylpolyglucocides with general formula R1O(R2O)b(Z)a, where R1—monovalent organic radical of from 6 to 30 carbon atoms; R2—divalent alkylene radical having from 2 to 4 carbon atoms; Z—sugar derivative containing 5 or 6 carbon atoms; b—natural number from 0 to 12, and a—natural number from 1 to 6.
There is a known method for producing immobilized enzymes through complexation reaction with molecular iodine and potassium iodide (RU 2157405 C2); as a result of complexation reaction, proteins are produced that contain bound iodine, and which from a solution pass to a solid phase state, i.e. water-insoluble complexes are formed. Solid phase state is characterized by the formation of polydisperse particles ranging in size from several micrometers to tens or hundreds of microns, which (the particles), in view of the large total surface area of zymophore able to interact with molecules of microbial substrates, ensure antimicrobial action of immobilized enzymes. Iodine that is a part of the complex provides a microbicide effect.
There is a known drug for administration of antiseptic agents, including halogen, into lower respiratory tract, containing at least one antiseptic in combination with support in the form of particles, obtained by known methods, and the carrier contains at least one liposomal preparation, microspheres sample, nanoparticles preparation, large porous particles preparation or molecules preparation, coated with polymer using a pulsating laser ranging in size from 1 to 30 microns (Patent RU 2212884 C2).
In all of the above known patents, authors did not set the task of synthesizing complex compounds with a given structure and properties, or excreting complex compounds from solutions and determining their composition and physical-chemical properties, which makes it hard to use complex iodine compounds with carbohydrates and proteins with biocidal properties as medicinal products. Moreover, the development of appropriate dosage forms, without a specific set of properties and qualities of complex iodine compounds—antibacterial agents, characterized by physical and chemical properties and composition, is hindered.
In recent years, some works devoted to exploration of the structure of complex compounds of carbohydrates with salts of magnesium, calcium and other complexing agents have appeared in scientific literature (O. Nimz, KGeβler, I. Uson, W. Saenger//Carbohydrate Research 2001. V. 336. P141-153.; M. Noltemeyer, W. Saenger//JACS 1980.V102:8.9.P.2710.; M. Noltemeyer, W. Saenger//Nature. 1976.V259. 26.P629).
Crystalline structure of a whole number of enzymes with having in its composition ions of magnesium, potassium, calcium, lithium, in their composition, i.e., metal salts, has been established. (Y. Goldgur, F. Dyda, A. B. Hickman, T. M. Jenkins, R. Craigie, D. R. Davies//Proc. Natl. Acid. Sci USA 1998. V95. No. 16. P.9150-9154.; F. Dyda, A. B. Hickman, T. M. Jenkins, A. Engelman, R. Craigie, D. R. Davies//Science. 1994. V266. P1981-1986).
At the same time there are no works involving a purposeful synthesis of iodine coordination compounds with a tailored nanoscale structure and, accordingly, tailored biocidal properties, suitable for implementation of a mechanism of action of these compounds.
Thus, the object of this invention is to create antibacterial agent (ABA) for the treatment of diseases of bacterial origin, including hospital acquired diseases and drug resistant TB.
Additional objectives of this invention are to develop a method for preparation of antibacterial agent and ABA-based drug to treat infectious diseases of bacterial origin.
Technical result of the invention is the increase ABA efficiency in vivo through activation of immunocompetent cells.